Mesenchymal stem cells transplantation suppresses inflammatory responses in global cerebral ischemia: contribution of TNF-α-induced protein 6

Abstract

Aim: To investigate the effects of mesenchymal stem cells (MSCs) transplantation on rat global cerebral ischemia and the underlying mechanisms. Methods: Adult male SD rats underwent asphxial cardiac arrest to induce global cerebral ischemia, then received intravenous injection of 5×10 6 cultured MSCs of SD rats at 2 h after resuscitation. In another group of cardiac arrest rats, tumor necrosis factor-α-induced protein 6 (TSG-6, 6 µg) was injected into the right lateral ventricle. Functional outcome was assessed at 1, 3, and 7 d after resuscitation. Donor MSCs in the brains were detected at 3 d after resuscitation. The level of serum S-100B and proinflammatory cytokines in cerebral cortex were assayed using ELISA. The expression of TSG-6 and proinflammatory cytokines in cerebral cortex was assayed using RT-PCR. Western blot was performed to determine the levels of TSG-6 and neutrophil elastase in cerebral cortex. Results: MSCs transplantation significantly reduced serum S-100B level, and improved neurological function after global cerebral ischemia compared to the PBS-treated group. The MSCs injected migrated into the ischemic brains, and were observed mainly in the cerebral cortex. Furthermore, MSCs transplantation significantly increased the expression of TSG-6, and reduced the expression of neutrophil elastase and proinflammatory cytokines in the cerebral cortex. Intracerebroventricular injection of TSG-6 reproduced the beneficial effects of MSCs transplantation in rats with global cerebral ischemia. Conclusion: MSCs transplantation improves functional recovery and reduces inflammatory responses in rats with global cerebral ischemia, maybe via upregulation of TSG-6 expression.

Anti-inflammatory cytokine TSG-6 inhibits hypertrophic scar formation in a rabbit ear model

“…TSG-6 expression in keloid scars is lower than in normal scars but higher than in normal skin; the expression and distribution of HA and IαI are consistent with those of TSG-6 (Lin et al, 2013). HA reduces scar formation by inhibiting fibroblast differentiation and decreasing inflammation, primarily by inhibiting prostaglandin E2 levels, inflammatory cell chemotaxis and oxygen free radical production (Mast et al, 1992;Schimizzi et al, 2006).…”

“…TSG-6 contains a hyaluronan-binding link domain and can form a stable covalent complex with inter-alpha-inhibitor (IαI), which is important in the protease network associated with inflammation. This antiinflammatory effect of TSG-6 has been confirmed in many studies (Getting et al, 2002;Lin et al, 2013;Nagyeri et al, 2011). In 2010, Tan showed that the anti-inflammatory factor TSG-6 was differentially distributed in keloid scars, normal scars and unscarred skin (Tan et al, 2011).…”

Metabolic Impact of Light Phase-Restricted Fructose Consumption Is Linked to Changes in Hypothalamic AMPK Phosphorylation and Melatonin Production in Rats

“…Stereotaxic coordinates were 0.8 mm (anteroposterior), 1.5 mm (lateral), and 4.0 mm (depth) [23]. The localization of the cannula was tested by evaluating the dipsogenic response to an intracerebroventricular (icv) angiotensin II injection (5 ng/μL saline; Sigma, St. Louis, MO, USA) 1 week after the surgical procedure (7th week of fructose treatment).…”

Preliminary Evidence of the role of estrogen and tamoxifen-induced regulation of complement proteins in rat hippocampus

“…Primer sequences were as follows: for C3, forward 5-CTGTACGGCATAGGGATATCACG-3, reverse 5-ATGCTGGCCTGACCTTCAAGA-3 (Misumi et al, 1990); for C1q, forward 5-ACCCAGACTTCCGCTTTCTG-3, reverse 5-CTTCAGGGGCCTCCTGTGTA-3 (selfconstricted); for β actin, forward 5-GCGCTCGTCGTCGACAACGG-3, reverse 5-GTGTGGTGCCAAATCTTCTCC-3 (Kit provided); for GAPDH, forward 5-CAAGGTCATCCATGACAACTTTG-3, reverse, 5-GTCCACCACCCTGTTGCTGTAG-3 (Lin et al, 2013); for C3a forward 5-GACCTACACTCAGGGC-3, reverse 5-ATGACG GACGGGATAAG-3 (Benard et al, 2004); for forward SYP 5-TCAGGACTCAACACCTCAGTGG-3 reverse 5-AACACGAACCATAAGTTGCCAA-3 (Chen et al, 2001).…”